Drug Abuse Methodology: Training and Interdisciplinary Application

描述(由申请人提供)：此K01申请响应PA-10-056，旨在为Rajeev I.Desai(PI)博士获得支持和“保护时间”，以便在非人类灵长类动物(NHP)静脉注射(IV)自我给药方法学的所有方面获得广泛的监督研究培训和经验。该项目旨在系统地让PI获得必要的技能和经验，以独立和专业地研究兴奋剂和其他成瘾药物的增强作用，并将该方法与体内同步微透析相结合，以测量相关的神经化学活动。K01奖项提供的支持最终将使PI能够：a)开发一个高度翻译的神经化学和行为研究的综合计划，以直接解决兴奋剂成瘾引起的公共健康问题，并开发治疗兴奋剂成瘾的药物；以及b)获得必要的工具，通过R01资助机制独立地继续和扩大这一研究领域。本项目的目的是通过一系列系统的实验来评估在简单和复杂的强化计划下静脉注射可卡因和尼古丁的自我给药行为，以优化PI的训练体验。接下来，PI将把他现有的专业知识与体内微透析技术结合起来 他新获得的行为技能，以测量在不同时间表条件下静脉注射自我给药期间，可卡因和尼古丁产生的纹状体多巴胺水平的变化。最后，将进行研究，以确定尼古丁激动剂为基础的候选药物是否减弱自我给药尼古丁或可卡因的强化和神经化学效应。该项目中拟议的研究将使PI成为一名训练有素、独立的年轻科学家，有资格在NHP进行高度翻译性成瘾研究。此外，计划中的研究可能会导致有希望的基于尼古丁的新型药物疗法的进一步发展，以帮助对抗困扰我们公共健康的兴奋剂成瘾的祸害。

DESCRIPTION (provided by applicant): This K01 application responds to PA-10-056, and is intended to obtain support and "protected time" for Dr. Rajeev I. Desai (PI) to gain extensive supervised research training and experience in all aspects of intravenous (IV) self-administration methodology in non-human primates (NHP). The project is designed to systematically allow the PI to acquire necessary skills and experience to independently and expertly study the reinforcing effects of stimulant and other addictive drugs, and to couple this methodology with concurrent in vivo microdialysis to measure related neurochemical activity. The support provided by the K01 award will ultimately allow the PI to: a) develop a comprehensive program of highly translational neurochemical and behavioral studies to directly address the public health concern of stimulant addiction and the development of medications for its treatment; and b) acquire the tools necessary to independently continue and expand this line of research through R01 funding mechanisms. The aims of this project are designed to optimize the PI's training experience through a systematic series of experiments evaluating IV cocaine and nicotine self- administration behavior under simple and complex schedules of reinforcement. The PI next will couple his existing expertise with in vivo microdialysis techniques to his newly acquired behavioral skills to measure changes in striatal dopamine levels produced by cocaine and nicotine during IV self-administration performance under different schedule conditions. Finally, studies will be conducted to determine whether nicotinic agonist-based candidate medications attenuate reinforcing and neurochemical effects of self- administered nicotine or cocaine. The proposed research in this project will establish the PI as a well-trained and independent young scientist who is qualified to conduct highly translational addiction research in NHP. In addition, the planned studies may lead to the further development of promising novel nicotinic-based pharmacotherapy to help combat the scourge of stimulant addiction that plagues our public health.